
Welcome. 
So, today we want to continue our 
discussion of homeostasis, and in 
particular you want to look at the 
regulatory mechanisms that allow the body 
to maintain homeostat homeostasis. 
Our learning objectives are going to be 
first that we're going to contrast reflex 
and local homeostatic control. 
Secondly, we wanted to find the 
components of the reflex loop. 
Third, we want to explain negative and 
postive feedbacks with are regulatory 
loops that are used to control 
homeostasis. 
Four, explain tonic and antagonistic 
controls. 
And then five, we want to explain 
circadian rhythms. 
And this is going to give us an overview 
of all the mechanisms we're going to deal 
with but one by one but within each 
individual organ system. 
Each system has a specific method that 
it's going to use to maintain 
homeostasis. 
So, all of these will not be common to 
the organ systems. 
But that each system for instance will 
use this specific type of control system. 
And so as you go through the course then, 
you'll be able to come back and look at 
this lecture and recognize the specific 
concept or specific mechanism that's 
being applied. 
Okay, so what are we talking about with 
homeostatic controls? 
So, first of all, we have homeostatic 
controls that's, that's affected at a 
local level. 
And this local response then, is 
occurring with neighboring cells. 
So, the first is we have cell one and we 
have cell two. 
The cell one secrete a chemical and this 
chemical then acts on cell two, which has 
a protein or a, what's called a receptor, 
which combined the chemical and become 
activating by the chemical and it just 
gives it a response. 
This type of control sort of para control 
where one neighboring cell is governing 
the actions of a second neighboring cell. 
We can also have a system where cell 
number two is, is secreting a chemical 
where that chemical feeds back on itself 
and regulates itself, its own activity. 
And that's called an autocrine control. 
So, we, we will see these autocrine 
controls and the, and the paracrine 
controls, and particularly when we are 
looking at the gastrointestinal track. 
We also have for local controls what are 
called gap junctions. 
And with gap junctions the two cells are 
physically connected there is a bridge 
between the two cells and this bridge is 
called the gap junction or nexus. 
This little opening this, which is common 
to the two cells allows ions to flow from 
one cell to another. 
And in particular, we will see that we 
can move the calcium from cell one to 
cell two, and that this will occur within 
the cardiovascular system. 
It allows the entire all cardiac muscle 
cells to act as a single sheet. 
So, that they will all contract in 
unison. 
And all relax in unison. 
And it'll be dependent upon the amount of 
calcium, which is being delivered across 
this across the gap junctions and through 
all the cells. 
So, those are going to be our local 
responses. 
But for most of the, of the course, we're 
going to be talking about the reflex 
loops. 
The reflexes or the reflect loops are 
where the response is made at a distance 
form the target cell. 
And the target cell is a cell that can 
respond to whatever the signal is that's 
being, that's being released. 
These cells, the cells that we're talking 
about are all the cells of the body. 
There's some millions of cells within the 
body and we have to be able to have the 
cells communicating with one another so 
that they can have an organized or 
regulated function within the body. 
Two major communications systems are the 
endocrine system and the nervous system. 
And that's what's diagrammed here. 
So, in the endocrine system we have a 
cell, which is the endocrine cell, which 
secretes a chemical. 
And this chemical is secreted into the 
bloodstream. 
That che, that chemical is then delivered 
by the bloodstream to cells, which have 
receptors on them, that is proteins on 
their surfaces. 
Or internal to the cell, which can 
recognize the chemical, and these are 
called the target cells. 
So, the endocrine cell is then regulating 
the activity of the target cells through 
this secreted chemical. 
In the case of the neuron, we have then a 
cell, which actually butts up against the 
second cell in an area, which is called 
the synapse. 
And this is a very, very small space. 
The neuron will secrete its chemical into 
the small space and this chemical is 
called a neurotransmitter. 
The chemical will act on the effector 
cell. 
That is the second cell in the series. 
And this cell could be a neuron, it could 
be a gland cell from a gland or it could 
be a muscle cell. 
Whatever the cell, the effector cell or 
target cell is, it has a receptor, which 
can recognize the chemical that's being 
released by the neuron. 
and then can, then, it binds, to this, to 
this receptor and causes the effector 
cell then to have some change in its 
activity. 
In both the endocrine cell and in the 
nervous system, what we're governing is 
our cells at a distance from the 
originating signal. 
So, they're called reflexes. 
So, if you recall the last time we met we 
said that the reflex loops had 
specifically three components. 
The first was a sensor that recognizes 
the stimulus so that we have some kind of 
an input which is coming into the body. 
So, this is called an afferent path. 
It's an inward path to the body, and this 
sensor detects that specific signal, and 
then sends that information to the 
integration center, which is the second 
component in the loop. 
And that's going to be usually the brain. 
And this is where we have our set point. 
So, the brain already has a set point 
within it, that then examines the input, 
inputting signal and evaluates whether it 
is higher, the same as the set point or 
lower than the set point. 
If the, is different from the set point, 
then the integration center sends out an 
efferent signal. 
This is an efferent path or a, er, or a 
path that's going outward from the 
integration center. 
And it's to the effectors. 
And the effectors are what's going to 
act, to cause the response. 
And this response then will take care of 
the stimulus. 
And in most cases, the response 
eliminates the stimuls, and under those 
conditions this would be called a 
negative reflex loop. 
And we'll talk about those in just a few 
minutes. 
So, let's just consider just in general a 
case that, that exemplifies these reflex 
loops. 
And the first of this would be we have an 
external change to the body. 
So, the body now, you were leaving your 
room, and you're going into, you're going 
outside and it's snowing outside and so 
it's very, very cold. 
And as you're standing outside and you 
don't have a coat on. 
Your body starts to lose heat. 
And as it does so, it's temperature will 
drop from 37 degrees, which is its normal 
temperature, to lets say 34 degrees 
Celcius. 
So, as the body is cooling then, these 
signals are being being sensed or, or are 
being detected by peripheral thermal 
sensors, which are present along the 
skin. 
And also, within the body, along the 
core, where it's detecting the, the, 
temperature of the blood. 
So, we have both these peripheral thermal 
sensors, as well as central thermal 
sensors, which will then send the 
information to the brain, to our 
integrating center. 
And this in an area called the 
hypothalamus. 
This area has a set point for body 
temperature, which says that the body 
temperature should be 37 degrees 
centigrade. 
And obviously, the input signal is 34, 
which means that the body is cold. 
The integration center of the brain 
recognizes the body is cold and sends out 
an efferent along an efferent pathway an 
efferent signal, to the effectors. 
And in this condition we have multiple 
effectors, one, we have skeletal muscle, 
skeletal muscle will start shivering, it 
contracts and relaxes, and contracts and 
relaxes. 
And as it's doing so you're shivering to 
generate heat. 
The second is that on the blood vessels, 
which are profusing the skin, the blood 
vessels which are directly underneath the 
skin are then, the blood is constricted. 
And as we move from that area to a deeper 
portion of the body or a deeper portion 
of the skin, so we do not lose as much 
heat from radiation. 
So, we have vasoconstriction, vaso 
meaning blood vessels, are constricted 
and we're moving blood away from the 
surface, right underneath the surface of 
the skin, into a deeper layer of the 
body. 
So, we don't lose as much heat then from 
the body through the skin. 
In addition to that, we concur a lot so 
that we actually decrease the amount of 
surface that's, that's radiating heat. 
And then obviously we can turn around and 
go back in the house, put on a coat, put 
on a sweater. 
And then go back outside or stay in the 
house where it's nice and warm and the 
body then will will warm up. 
The effectors then, are, are going to 
generate heat. 
So, as they increase heat, we will 
eliminate our stimulus, which was that 
the body temperature was low, and bring 
the body temperature back up to normal, 
which is 37 degrees. 
Exactly analogous to the thermostat, 
which is within your house. 
Well, what about internal changes? 
So, we can also have an internal change. 
For instance, you get an infection and 
this infection will activate a cell 
called a macrophage. 
The macrophage secretes a, a chemical, 
which is called a pyrogen. 
And the pyrogen acts on the hypothalamus, 
the same se, the same area of the brain 
that was active when we were having an 
input from the thermal receptors in the 
skin when we were outside in the cold. 
This area of the hypothalamus, where our 
original set point was 37 degrees, but in 
the presence of the pyrogens, the set 
point is now 40 degrees centigrade. 
The body is now the set point is now 40 
degrees centigrade. 
But the, the input stimulus, which is 
coming back to the hypothalamus from the 
skin and from the core temperature of the 
blood is saying that the body is at 37. 
And so, the brain then interprets the 
body as being cold. 
It will send out an effector signal to 
the effectors, which area again our 
skeletal muscle. 
Skeletal muscle will start to shiver, we 
will have contraction and relaxation to 
generate heat, and we will have 
vasoconstriction of the of moving blood. 
Then away from the surface, underneath 
the surface of the skin into deeper areas 
so that we do not radiate as much heat. 
The consequence is that we generate heat. 
The body starts to warm, and as the body 
starts to warm, it then is moving from 37 
to 40 degrees. 
It's exactly the same reaction that we 
had when we were, we were going outside 
in the cold. 
The body is responding in exactly the 
same way. 
The difference here is that the set point 
has been reset. 
And this is an important point to 
remember, because often when the body has 
a pathological condition, it is trying to 
do something, which it normally would do 
to, to rectify a situation. 
It may be, in fact, responding to a set 
point that has been set to a higher 
level. 
And so this actually causing a, a 
malfunctioning within, within the system 
itself. 
Alright, so most the reflex loops that 
we're going to be talking about in, 
throughout this course are going to be 
these negative feedback loops. 
Or feedback loops which remove the 
initiating stimulus. 
The negative feedback loops can be 
simple. 
And that's what's diagrammed here, where 
the stimulus is received by, for 
instance, an endrocine cell. 
That endocrine cell secretes, secretes a 
hormone or a chemical, which works on the 
target cell and then it removes the 
stimulus. 
The initiating stimulus. 
So, what do we have an example of this. 
You just finished lunch and as you 
finished lunch then you ate a lot of 
rice. 
And the rice has now been digested by the 
gastrointestinal tract, and so glucose, 
the amount of glucose in the blood has 
risen. 
So, an increase in plasma glucose levels 
then will cause an increase of will act 
on the beta cells of the pancreas and 
cause the release of insulin. 
Insulin is a hormone, which acts on 
skeletal muscle and, and it makes the 
skeletal muscle take up that glucose into 
the skeletal muscle removing it from the 
blood so that it's taking it into the 
skeletal muscles for storage. 
And as it does so then the plasma glucose 
levels will fall. 
Okay, so we are removing then the 
initiating signal. 
The negative feedback loops can be also 
very complicated, and this we'll see when 
we talk about the hypothalamus pituitary 
endocrine feedback loops. 
For instance, that's what's shown here, 
where we have a stimulus and the stimulus 
works on the first cell, this cell 
secretes a chemical A. 
And that chemical works on the second 
cell B, which stimulates the secretion of 
the chemical B. 
And it then works on C, which then 
eventually works on cell D and there is 
negative feedbacks to each of these, to 
each of these levels. 
So, that each level then is turned off by 
the by the stimulated chemical. 
So, do we have an example of this? 
Well, temperature. 
So again, we have a system where we have 
our temperature, the body is falling and 
when temperature the body is falling. 
Then the hypothallamus, the brain, will 
cause a release of a hormone, which is 
called a thyroid releasing hormone. 
And this hormone works on the pituitary, 
another region of the brain which 
releases thyroid stimulating hormone, 
which then acts on thyroid hormone gland. 
This gland will secret thyroid hormone 
and the thyroid hormone acts on all the 
cells of the body to increase the 
metabolism of all the cells of the body. 
And in doing so, then it revs up the 
generation of heat. 
So, this is a simple this is a very 
complex reflex loop, a negative reflex 
loop. 
But again by generating heat, we then 
remove our initiating initiating sis, 
signal, which was low temperature. 
Now, in some instances, we'll see 
positive feedbacks. 
Positive feedbacks don't occur in very, 
very many locations but we will see this 
in the female reproductive tract, for 
instance. 
Where where we will have an instance 
where the the cell is going to, to have 
an endocrine cell secreting a hormone 
called follicle-stimulating hormone. 
Which acts on the target cell to increase 
the receptors for follicle-stimulating 
hormone on that target cell. 
So, all of these follicle-stimulating 
hormone receptors then increase in 
number, making the target cell very, very 
sensitive to the FSH. 
So, that's one way to have a positive 
feedback, where you're increasing the 
sensitivity of the target cell. 
Another way to do this is that we simply 
have the first target cell, then secretes 
something, which causes more of the 
initiating signal to increase. 
And this is what's characteristic of the 
clotting system in your blood. 
So that when we start that cascade, that 
cascade is a cascade of proteases, and 
these proteases then feed back and 
activate those cells so that you have an 
accelerating system. 
So, you get more and more and more and 
more and more of the fibrin clot. 
Obviously you don't want the entire blood 
stream to clot and so there has to be a 
way to turn off the positive feedback. 
And the way to do so is through a 
negative feedback loop. 
Now there are a couple of more things we 
want to consider, just very briefly and 
then when we come to the, within the 
organ systems themselves we'll talk about 
it in more detail. 
But these the systems that we've been 
talking about to date have been things 
where we turn something on and we turn 
something off but under the condition of 
tonic control. 
Now, we're just modulating the activity 
of the, of a specific cell. 
We're never really turning it off and 
we're never really turning it on. 
And a tonic control is exemplified by the 
smooth muscle cells, which are lining the 
around the lumen of a blood vessels such 
as your arteries and your arterials. 
Under normal conditions in the body, 
those cells, those smooth muscle cells 
have a basal state of contraction. 
So, that they, that the lumin of the 
vessel is not completely open or 
completely closed. 
And that's what's shown here, that's our 
basal state. 
If I increase the sympathetic nervous 
system activity to these smooth muscle 
cells, I can cause the cells to contract 
and when they do so, they will, they will 
make this lumen of the vessel. 
So, they will decrease the size of the, 
of the lumen and that's through increased 
input from the sympathetic nervous 
system. 
So, this is called vasoconstriction. 
Vaso for the blood vessel, constriction. 
We are causing contraction of the smooth 
muscle, which is around that lumen and 
making the lumen smaller. 
I can decrease the input from the 
sympathetic nervous system. 
And by doing so then the smooth muscle 
cells will relax and then the volume, the 
lumen of the vessel will then open. 
And this is called vaso dilation. 
Vaso again meaning blood vessel and we're 
dilating. 
So, opening the lumen of the vessel. 
So, if you notice a couple a things. 
One is, is that we're not turning on or 
off the system at any one time. 
We're simply modulating how much activity 
we have in the sympathetic nervous 
system. 
And the second thing is, is that we, have 
a situation where the smooth muscle can 
hold a specific state of contraction for 
a very long periods of time. 
And this tonic, long, long held 
contraction, which is unique to smooth 
muscle. 
We couldn't do this with skeletal muscle 
and can't do this with cardiac muscle. 
But with smooth muscle, you can hold the 
contractal state for very long periods. 
So, this is called tonic control. 
and the tonic control, the one way to 
think about is as thinking of a, a radio 
dial where you can dial up the volume and 
you can dial down the volume of the 
sound, but that you never actually turn 
it off. 
Now in the, in the in the body we also 
have antagonistic control, which is 
mediated by the nervous systems. 
And then, and we have essentially two 
types of peripheral nervous systems that, 
to deal with. 
One is called the parasympathetic and the 
other is the sympathetic. 
On the heart, we have input from both the 
parasympathetic and the sympathetic. 
And the two nervous systems are going to 
work in opposite directions or in an 
antagonistic manner. 
They're in, they are not binding to the 
same receptors, but they are working in 
opposite control. 
The parasympathetics are going to slow 
the heart rate, so that if a normal heart 
rate is 100 beats per minute. 
That's our intrinsic heart beat. 
Then the parasympathetics will slow it to 
less than 100 beats per minute. 
This would be what you would see with a 
very highly trained athlete. 
Somebody like Lance Armstrong, for 
instance. 
They can have a heart rate that's 35 
beats per minute. 
I have a heart rate that's 80 beats per 
minute. 
So, 35 beats per minute is a very, very 
low heart rate. 
They have a very high parasympathetic 
tone. 
We also have situations where we need to 
increase our heart rate. 
So, when we start running, or we're going 
swimming, we have to have a higher output 
of blood from the heart. 
We have to increase our cardiac output, 
and that's going to be by using the 
sympathetic nervous system. 
And under these conditions we can 
increase our heart rates so that we go 
above 100 beats per minute. 
So, we're stimulating the heart to 
increase it. 
And as we talk about the cardiovascular 
system, we'll describe exactly the 
mechanisms by which these two, these two 
nervous systems are able to control a 
heart rate. 
And then the last thing that I want to 
talk about is our circadian rhythms. 
Circadian rhythms are where biological 
biological systems in your body are 
changing on in a on a 24 hour cycle or 24 
hour basis without any input from you. 
This is on an automatic, rhythmic kind of 
situation. 
When you go to sleep at night for 
instance your body temperature will drop. 
And then when you awaken in the morning 
it will rise again, and the drop is only 
a couple of degrees, but why you're 
sleeping you have a lower base level 
metabolic rate. 
Body temperature will fall. 
The other one that we see that's 
regulated by rhythms or circadian rhythms 
are hormones. 
And so, we have two hormones that are 
diagrammed here, one is growth hormone. 
Growth hormone is released during early 
sleep. 
And then it, it falls, at, to more basal 
levels when we're waking up. 
Well, cortisol, a second hormone 
increases well, your, just before you 
wake up. 
Cortisol and growth hormone are both 
activating glucose levels. 
As you're sleeping you have fasting, and 
so glucose, blood glucose levels can 
fall. 
And these two hormones are raising blood 
glucose levels. 
The growth hormone raises the blood 
glucose level by having a signal coming 
from the empty stomach, which is another 
hormone called ghrelin, and it turns on 
this, this secretion of growth hormone. 
The growth hormone raises blood glucose 
and then cortisol also comes on and 
raised blood glucose further. 
And this very high blood glucose level 
actually turns off. 
The growth hormone signal. 
So, growth hormone is regulated by low. 
It's turn on by low blood glucose, and 
it's turned off by high blood glucose 
levels. 
So, these circadian rhythms occur without 
us thinking about it. 
And you're all very familiar with them. 
for instance, when you are traveling then 
you move from, let's say you're going 
from New York to London. 
You go through time zone and when you 
arrive in London, then you're six hours 
off from, from your normal your normal 
time zone. 
The [UNKNOWN] for about two days, a day 
24 hours to 48 hours, you feel a little 
odd. 
You feel a little off. 
You're hungry when other people are not 
hungry. 
You want to sleep when other people don't 
want to sleep. 
and then eventually your body sort of 
accustom, gets accustom to the time zone 
that you're now out functioning in. 
What has happened is that your body has 
reset the set points. 
So, they reset the set points for the 
circadian rhythms. 
And when you reset the set points. 
You reset the set points not only for 
temperature but also for cortisol. 
And for growth hormone. 
And for all of the other. 
all the other factors which are being 
governed by the circadian rhythm. 
And it takes a little while for the body 
to reset the set point. 
And what resets the set point is 
sleep-wake. 
These are cycles which are dictated by 
sleep-wake and not by light-dark inputs. 
So, what about people who are known to be 
night owls? 
And what about people who are early 
birds? 
What do I mean when I'm talking about 
night owls and early birds? 
Are you a night owl or are you an early 
bird? 
Night-owls are those who can stay up all 
night long, they've got plenty of energy 
and at 4 o'clock at the morning they're 
about ready to go to bed. 
But they certainly have a hard time to 
wake up at 8 o'clock in the morning, 
because when they wake up at 8 o'clock in 
the morning and they feel cold. 
They can't think very clearly. 
They're looking for their coffee. 
They can't find their shoes. 
So, they're off. 
They're not happy. 
The, the early bird is the converse. 
The early bird wakes up at 5 o'clock in 
the morning. 
They're, they're ready to go. 
They're full of energy. 
Their, their body is warm. 
They one find their coffee, they find 
there shoes, everything, and they're out 
and running. 
So, the difference between these two, 
these are both normal people, but the 
difference between them is that their 
circadian rhythms are different. 
So, circadian rhythms can vary depending 
upon an individual, and then not nessarly 
pathological if you were a night owl or 
if you're an early bird. 
I have a good friend who lived for many, 
many years in Seattle, and he has now 
lived, for something like 20 or 30 years 
in, in Durham, North Carolina, which of 
course is a different time zone. 
And he has yet to change his circadian 
rhythm. 
His circadian rhythm is still based on 
Seattle time. 
Alright, so, one of our general concepts. 
So, the general concept is first we have 
stability of our internal variable is 
achieved by balancing our inputs and 
outputs to the body. 
And among the organ systems. 
Second, we have in a negative feedback 
system, the change in the variable is 
corrected by bringing the body back to 
the initial set point. 
However, the set points can be reset, and 
this is an important point. 
We can reset them. 
When we're resetting out circadian 
rhythms but we can also reset them to to 
tolerate higher sodium within the body or 
or to tolerate lower temperatures. 
Or to tolerate lower blood pressures, or 
higher blood pressures. 
So, the circa, so the set points then are 
modified. 
And then thirdly, it's important to 
remember that it's not always possible to 
maintain everything relatively constant. 
There's going to be a hierarchy in the 
maintenance of life. 
And again, the brain is going to win. 
The brain wants blood, the brain gets 
blood, and it will shut down the 
circulatory system to profusion of all 
the other organs. 
The brain and the heart, okay, win. 
Alright, so the next time we come in here 
we're going to talk about some more about 
the balances of these fluid compartments 
and how we move materials from one 
compartment to another. 
Alright, see you then. 

